The role of opsonic alpha 2SB glycoprotein as a factor regulating macrophage activity during experimental tumor growth was investigated. Parallel studies have also been done in patients with lung cancer to assess the serum level of opsonic alpha 2SB glycoprotein following BCG immunotherapy. The opsonic protein from mouse, rat and human serum has been isolated and an immunoassay for its measurement has been developed. Opsonic alpha 2SB glycoprotein is identical to cold-insoluble globulin or plasma fibronectin. Both proteins have identical molecular weights, manifest ability to stimulate particulate phagocytosis, and demonstrate heparin dependency in terms of biological activity. In vivo assessment of opsonin levels during tumor growth utilizing the Sarcoma 180 tumor model in mice demonstrated that with an increase in tumor growth there is an elevation in immunoreactive opsonic protein, but a decrease in the bioassayable activity of the plasma. Reticuloendothelial phagocytic activity was also measured during Sarcoma 180 tumor growth and activation of macrophage clearance was associated with increased hepatic Kupffer cell activity. Patients with lung cancer after lung resection but prior to BCG therapy demonstrated heightened levels of opsonic protein as measured by immunoassay. This heightened level post-operation was typical to rebound hyperopsonemia after surgery. With BCG, a normalization of opsonin levels was observed. Thus, macrophage activity may be, in part, modulated by circulating opsonin or plasma fibronectin but the association of cell bound fibronectin to phagocytic activity is yet to be determined. Also, during tumor growth there may be an inhibition of bioassayable opsonin activity even in the face of elevation of immunoreactive protein.